Patent EA-003941-B1 (EA)
Title: 2-aminopyridines containing fused ring substituents
Inventor: LOWE JOHN ADAMS III
IPC: C07D213/73
Filed: 2000-02-02
Abstract: 1. A derivatives 2-aminopyridines of the general formula 1 or its pharmaceutically acceptable salts wherein A and B is a ring fused with phenyl ring, the mentioned ring is a saturated or unsaturated ring with 5-7-membered atoms wherein from one to two of the ring members are heteroatoms selected, independently, from N, O and S, with the proviso that no two adjacent ring members can both be heteroatoms; X is oxygen or a bond; Y is (C1-C6) alkylene; R <1> is hydrogen, (C1-C6)alkyl or (C1-C6)alkyl substituted -NR<2>R<3>, wherein R<2> and R<3> are selected independently from the group consisting of N, alkyl, aryl, aralkyl or tetrahydronaphtalene, wherein said aryl group or indicated aryl moiety of the mentioned aralkyl group is phenyl or naphthyl, indicated alkyl group or indicated alkyl moiety of the mentioned aralkyl group contains from one to six carbon atoms and is straight or branched, and indicated aryl group, said tetrahydronaphthalene or said aryl moiety of the mentioned aralkyl group may optionally be substituted with from one to three substituents, that are selected from halogen, nitro, cyano, amino, (C1-C4)alkoxy, (C1-C4)alkylamino group, or R<2> and R<3> together with nitrogen to which they are attached forms heterocyclic ring or cyclic or bicyclic ring which is saturated or unsaturated. 2. A compound according to claim 1 formula 1 wherein heterocyclic ring, formed from R<2> and R<3> is piperidine, azetidine, piperazine and pyrrolidine, wherein said piperidine, azetidine and pyrrolidine may optionally be substituted with one or more substituents, that are independently selected from the group consisting of (C1-C6)alkyl, amino, (C1-C8) alkylamino, [di-(C1-C6)alkyl]amino, phenyl substituted 5 to 6 membered heterocyclic rings containing from 1 to 4 rings nitrogen atoms, benzoyl, benzoylmethyl, benzylcarbonyl, phenylaminocarbonyl, phenylethyl and phenoxycarbonyl group, and wherein the phenyl moieties of any of the foregoing substituents may optionally be substituted with one or more substituents, that are independently selected from halogen, (C1-C3)alkyl, (C1-C3)alkoxy, nitro, amino, cyano, CF3 and OCF3; 3. A compound according to claim 1, wherein R<1> and R<2> together with nitrogen to which they are bound, forms 6-amino-3-azabcyclo[3.1.0]hex-2-il formulas: wherein R<4> and R<5>, each independently selected from the group consisting of hydrogen, (C1-C6)alkyl, phenyl, naphthyl, (C1-C6)alkyl-C(=O)-, HC(=O)-, (C1-C6)alkoxy-(C=O)-, phenyl-C(=O)-, naphthyl-C(=O)-, and R<6>R<7>NC(=O)- wherein R<6> and R<7> are selected, independently, from hydrogen or (C1-C6)alkyl. 4. A compound according to claim 1, wherein A and B together forms a ring fused with phenyl ring. 5. A compound according to claim 4, wherein fused ring and phenyl ring include naphthalene group. 6. A compound according to claim 1, wherein X is oxygen. 7. A compound according to claim 1, wherein Y is -CH2CH2-. 8. A compound according to claim 1, wherein R<1> is (C1-C6)alkyl group substituted with -NR<2>R<3>. 9. A compound according to claim 1, wherein R<1> is 2-substituted with -NR<2>R<3> ethyl group. 10. A compound according to claim 7, wherein R<2> and R<3> together with nitrogen to which they are attached, form heterocyclic ring, that are selected from the group consisting of 3-azabcyclo[3.1.0]hexyl, piperidine and piperazine. 11. A compound according to claim 10, wherein a ring is 3-azabcyclo[3.1.0]hexyl ring. 12. A compound according to claim 7, wherein each of R<2> and R<3> independently is a methyl or propyl. 13. A compound according to claim 1, wherein A and B together forms a ring fused with phenyl ring, fused ring and phenyl ring together include naphthalene group, X is oxygene, Y is CH2CH2-, R<1> is R<2>R<3>NCH2CH2-group and R<2> and R<3> together form a ring, that is selected from azabcyclohexane, piperidine and piperazine, or R<2> and R<3> each independently is methyl, ethyl and propyl. 14. A compound according to claim 1, selected from the group consisting of 1-[4-(6-aminopyridine-2-il)naphthalene-1-iloxymethyl]cyclohexanol; 6-[4-(2-(2-dimethylaminoethoxy)ethoxy)naphthalene-1-il]pyridine-2-ilamin; 6-[4-(2-hydroxyethoxy)-5,6,7,8-tetrahydronaphthalene-1-il]pyridine-2-ilamin. 15. A compound according to claim 1 of the formula I-a: wherein dotted line is an optional bond; Y is (C1-C6)alkylene; R<1> is hydrogen, (C1-C6)alkyl or (C1-C6)alkyl, substituted -NR<2>R<3>, wherein R<2> and R<3> are selected independently from the group consisting of N, alkyl, aryl, aralkyl or tetrahydronaphtalene, wherein said aryl group or said aryl moiety of the mentioned aralkyl group is phenyl or naphthyl, indicated alkyl group or indicated alkyl moiety of the said aralkyl group contains from one to six carbon atoms and is straight or branched, and said aryl group, mentioned tetrahydronaphthalene or said aryl moiety of the mentioned aralkyl group, optionally substituted with substituents from one to three, that are selected from halogen, nitro, cyano, amino, (C1-C4)alkoxy and (C1-C4)alkylamino group, or R<2> and R<3> form together with nitrogen to which they are attached, heterocyclic ring or cyclic or bicyclic ring, that is saturated or unsaturated. 16. A compound according to claim 1, selected from the group consisting of 6-[4-(2-(2-diethylaminoethoxy)ethoxy)naphthalene-1-il]pyridine-2-ilamin; 6-[4-(2-(2-dipropylaminoethoxy)ethoxy)naphthalene-1-il]pyridine-2-ilamin; 6-[4-(2-(2-(N-methyl, N-benzyl)aminoethoxy)ethoxy)-naphthalene-1-il]pyridine-2-ilamin; 6-[4-(2-(2-(1-piperidinyl)ethoxy)ethoxy)naphthalene-1-il]pyridin-2-ilamin; 6-[4-(2-(2-(N-methylpiperazine-4-il)ethoxy)ethoxy)naphthalene-1-il]pyridine-2-ilamin and 6-[4-(2-(2-(6-amino-3-azabicyclo[3.1.0]hex-2-il)ethoxy)ethoxy)naphthalene-1-il]pyridine-2-ilamin.